V M Tronnier

Universität zu Lübeck, Lübeck Hansestadt, Schleswig-Holstein, Germany

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Publications (81)365.77 Total impact

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    ABSTRACT: Retinoic acid (RA) is required for development and homeostasis of the normal mammalian brain and may play a role in the initiation and progression of malignant brain tumors, such as the glioblastoma multiforme (GBM) and the gliosarcoma (Gsarc). The subpopulation of stem-like glioma cells (SLGCs) was shown to resist standard glioma radio-/chemotherapy and to propagate tumor regrowth. We used phenotypically distinct, self-renewing SLGC lines from six human GBMs, two Gsarcs, and two subcloned SLGC derivatives in order to investigate their responsiveness to atRA and to identify the RA-receptor (RAR) isotypes involved. In general, atRA exerted a pro-proliferative and pro-survival effect on SLGCs, though the efficacy was distinct. By means of RAR isotype-selective retinoids we disclosed that these effects were mediated by RARα and RARγ, except for one SLGC line, in which the pro-proliferative signal was induced by the RARβ-selective retinoid. Only one GBM-derived cell line (T1338) and a subpopulation of another (T1389) displayed neural differentiation in response to atRA. Differentiation of T1338 was induced by RARα and RARγ isotype-selective retinoids, associated with down-regulation of Sox2, and the failure to induce orthotopic tumors in the brains of SCID mice. The differential responsiveness of the SLGC lines appeared unrelated to the expression of RARβ, as (i) atRA augmented RAR isotype mRNA expression and particularly rarβ mRNA in all SLGC lines, (ii) rarβ promoter hypomethylation in the SLGC lines was not related to differentiation and (iii) the induction of T1338 differentiation was by RARα- and RARγ-selective ligands.
    Neuroscience 08/2014; · 3.12 Impact Factor
  • Kai Bötzel, Volker Tronnier, Thomas Gasser
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    ABSTRACT: Essential tremor is the most common type of tremor, with a prevalence of 0.4% in the overall population and 4-7% in persons over age 65. In general, tremor is so common that patients with tremor are frequently treated not only by neurologists, but also by physicians from other specialties. This review is based on publications retrieved by a selective PubMed search and on guidelines from Germany and abroad. Particular tremor syndromes are usually diagnosed on the basis of their typical clinical presentation and whatever accompanying manifestations may be present. Ancillary tests are usually unnecessary. Unilateral rest tremor accompanied by rigidity and bradykinesia is typical of Parkinson's disease. Essential tremor is a bilateral postural tremor. The most common cause of intention tremor is multiple sclerosis. Mild tremor syndromes can often be treated satisfactorily with drugs. In case of severe tremor, which is rarer, a stereotactic operation can be considered. The usual outcome of such procedures is the complete suppression of tremor. Most patients with tremor can be given a precise diagnosis and offered specific treatment. It is important for the physician to inform the patient about the expected course of tremor over time, its possible genetic causes, and the various available treatments.
    Deutsches Ärzteblatt International 03/2014; 111(13):225-36. · 3.54 Impact Factor
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    ABSTRACT: This retrospective study investigated the outcome of patients with brain metastases after radiosurgery with special emphasis on prognostic impact of visible intratumoral necrosis on survival and local control. From 1998 through 2008, 149 patients with brain metastases from solid tumors were treated with stereotactic radiotherapy at Luebeck University. Median age was 58.4 years with 11%, 78%, 10% in recursive partitioning analysis (RPA) classes I, II, III, respectively. 70% had 1 metastasis, 29% 2-3 metastases, 2 patients more than 3 metastases, 71% active extracranial disease. Median volume of metastatic lesions was 4.7 cm3, median radiosurgery dose 22 Gy (single fraction). 71% of patients received additional whole-brain irradiation (WBI). All patients were analyzed regarding survival, local, distant failure and prognostic factors, side effects and changes in neurologic symptoms after radiotherapy. The type of contrast-enhancement in MR imaging was also analyzed; metastatic lesions were classified as containing necrosis if they appeared as ring-enhancing with central areas of no or minimal contrast enhancement. Median survival was 7.0 months with 1-year and 5-year survival rates of 33% and 0.4%, respectively. Tumor necrosis (ring-enhancement) was visible on pretreatment MRI scans in 56% of all lesions and lesions with necrosis were larger than non-necrotic lesions (6.7 cm3 vs. 3.2 cm3, p = 0.01). Patients with tumor necrosis had a median survival of 5.4 months, patients without tumor necrosis 7.2 months. Local control rate in the irradiated volume was 70%, median survival without local failure 17.8 months. Control in the brain outside the irradiated volume was 60%, median survival without distant failure 14.0 months. Significant prognostic factors for overall survival were KPS (p = 0.001), presence of tumor necrosis on pretreatment MRI (p = 0.001) with RPA-class and WBI reaching marginal significance (each p = 0.05). Prognostic impact of tumor necrosis remained significant if only smaller tumors with a volume below 3.5 cm3 (p = 0.03). Side effects were rare, only one patient suffered from serious acute side effects. Results of this retrospective study support that stereotactic radiotherapy is an effective treatment option for patients with metastatic brain lesions. The prognostic impact of visible tumor necrosis (ring-enhancement) on pretreatment MRI scans should be further investigated.
    Radiation Oncology 07/2013; 8(1):162. · 2.11 Impact Factor
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    ABSTRACT: Background: Cerebrospinal fluid (CSF) leaks are well-known and frequent complications of intracranial pro-cedures. Numerous studies have focused on the clinical aspects of incidence, risk factors, outcome, treatment, and prevention; however, large prospective multicenter studies are missing. The aim of this study was to prospec-tively analyze the rate of CSF leaks and their causes. Method: A total of 545 patients with a variety of intra-cranial procedures (elective and trauma) were recruited in a multicenter, prospective, observational study over a 12-month period. Results: In 545 cranial surgeries, we observed a CSF leak rate of 7.7% (n = 42) at the time of discharge from the hos-pital. Significant risk factors for CSF leaks were poste-rior fossa surgery, opened pneumatized spaces, patients younger than 66 years, size of craniotomies, craniecto-mies rather than craniotomies, remaining dura defects larger than 1 cm, and wound closure without using muscle sutures, continuous locked, or unlocked sutures. Non-significant risk factors for CSF leaks were revision crani-otomies, craniotomies for different pathologies, previous radiotherapy and/or systemic chemotherapy, augmenta-tion of dura sutures with various materials, and wound drains as well as temporary CSF drains. Conclusion: Despite the number of techniques and devel-opments for dural closure, the problem of CSF leaks remains evident and further improvement has to be made.
    Innovative Neurosurgery. 12/2012;
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    ABSTRACT: BACKGROUND: Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial. METHODS: In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259). FINDINGS: An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to -20·8 points (SD 17·1; -47·9%; n=40) at 6 months; -26·5 points (19·7; -61·1%; n=31) at 3 years; and -25·1 points (21·3; -57·8%; n=32). The improvement from 6 months to 3 years (-5·7 points [SD 8·4]; -34%) was significant and sustained at the 5-year follow-up (-4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae. INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. FUNDING: Medtronic.
    The Lancet Neurology 10/2012; · 23.92 Impact Factor
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    ABSTRACT: Background Severe forms of primary dystonia are diffi cult to manage medically. We assessed the safety and effi cacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial.
    The Lancet Neurology 01/2012; 11(12):1029-1038. · 23.92 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves quality of life (QoL) in PD. However, QoL fails to improve in a relevant proportion of patients. We studied clinical baseline and progression parameters associated with improvement in QoL after DBS. Data from a German randomized, controlled study comparing DBS (60 patients) with best medical treatment (59 patients) were analyzed. Changes in patients' QoL were assessed using the Parkinson's Disease Questionnaire (PDQ-39) at baseline and at the 6-month follow-up. For the STN-DBS patients, the changes in PDQ-39 were correlated with predefined clinical preoperative and progression parameters. Scores for QoL improved after STN-DBS for 57% of the patients, and for 43% patients, they did not improve. Patients with improvement in QoL showed significantly higher cumulative daily "off" time. Changes in the PDQ-39 showed a significant positive correlation with the cumulative daily off time at baseline. Logistic regression analysis revealed that 1 additional hour off time at baseline increases the odds for improvement on PDQ-39 by a factor of 1.33 (odds ratio). In the postoperative course, changes in the PDQ-39 significantly correlated with the reduction of cumulative daily off time, an improvement on the UPDRS (UPDRS III off), and positive mood changes. Among the baseline parameters, the cumulative daily off time is the strongest predictor for improvement in disease-related QoL after DBS. Improvement in QoL after STN-DBS is also correlated with changes in motor functions and changes in depression and anxiety.
    Movement Disorders 12/2011; 26(14):2516-21. · 5.63 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves quality of life (QoL) in Parkinson's disease (PD). Dementia is considered as a contraindication for STN-DBS. However, no controlled study assessed the impact of STN-DBS on the QoL and motor outcome in PD patients with a borderline global cognitive impairment. We studied clinical baseline and progression parameters in a cohort of STN-DBS patients with a global cognitive score still in the non-demented range but scoring in the lowest quartile of the Mattis Dementia Rating Scale (MDRS), a measure of global cognitive functioning. Data from a German randomised controlled study comparing DBS (60 patients) with best medical treatment (BMT, 59 patients) were analysed. Changes in patients' QoL scores were assessed using the Parkinson's disease questionnaire (PDQ-39) at baseline and at the 6 months follow up. Patients were split into four groups according to their MDRS performance at baseline and these groups were compared in the context of motor outcome and QoL. Twelve out of sixty patients of the STN-DBS group scored in the lowest quartile of the MDRS (range between one hundred thirty and one hundred thirty seven points). An individual analysis revealed that 3 of 12 patients showed a clinical relevant improvement in QoL whereas the group statistics did not reveal any significant improvement in QoL measures after STN-DBS compared to the BMT group. Since this failure to improve in QoL cannot be explained by a failure to improve in motor functions, stimulation settings and psychiatric scales after STN-DBS, the failure to improve in QoL in patients with a borderline global cognitive score might be specifically related to lower cognitive functioning.
    Journal of the neurological sciences 07/2011; 310(1-2):261-6. · 2.32 Impact Factor
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    ABSTRACT: The present paper introduces extensions to a novel model of tumour induced brain deformation in order to aid non-rigid registration of images displaying brain tumour pathology to a standard reference atlas. The model serves as a bio-physical prior and by that resolves the inherent irregularities that naturally arise in the considered registration problem. The proposed model is formulated in terms of a constrained optimisation problem. At this, the data term is modelled on the basis of the population density of cancerous cells obtained from the solution of an initial boundary value problem. A soft constraint allows for approximating bio-mechanical properties of brain tissue. It is demonstrated that introducing a non-linear weighting functional with respect to the computed density of cancerous cells into both – the data term and the soft constraint – allows for an adaptive control of the deformation pattern. Additionally, we explicitly penalise deformations of rigid structures and extend the numerical scheme by exploiting analytical derivatives as well as the compact support of the employed parametric deformation model during optimisation. Further, we have made available a strategy for re-orientation of diffusion tensors subject to spatial deformation.
    Proceedings of the 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2011, March 30 - April 2, 2011, Chicago, Illinois, USA; 01/2011
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    ABSTRACT: Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time.
    European Radiology 01/2011; 21(7):1517-25. · 4.34 Impact Factor
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    ABSTRACT: The treatment of refractory epilepsy by vagus nerve stimulation (VNS) is a well-established therapy option for patients not suitable for epilepsy surgery and therapy refractory depressions. To analyze surgical and technical complications after implantation of left-sided VNS in patients with therapy-refractory epilepsy and depression. One hundred five patients receiving a VNS or VNS-related operations (n = 118) from 1999 to 2008 were investigated retrospectively. At the time of operation, 84 patients were younger than 18 years, with a mean age of 10.5 years. Twenty (19%) patients had technical problems or complications. In 6 (5.7%) patients these problems were caused by the operation. The device was removed in 8 cases. The range of surgically and technically induced complications included electrode fractures, early and late onset of deep wound infections, transient vocal cord palsy, cardiac arrhythmia under test stimulation, electrode malfunction, and posttraumatic dysfunction of the stimulator. VNS therapy is combined with a wide spread of possible complications. Technical problems are to be expected, including electrode fracture, dislocation, and generator malfunction. The major complication in younger patients is the electrode fracture, which might be induced by growth during adolescence. Surgically induced complications of VNS implantation are comparably low. Cardiac symptoms and recurrent nerve palsy need to be taken into consideration.
    Neurosurgery 12/2010; 67(2 Suppl Operative):489-94. · 2.53 Impact Factor
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    ABSTRACT: A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains "global cognitive functioning," "memory," "working memory," "attention," and "executive function." These domain-specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN-DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa-equivalence dosage (LED) and axial subscore of the UPDRS in the off-medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN-DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN-DBS.
    Movement Disorders 08/2010; 25(11):1583-9. · 5.63 Impact Factor
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    ABSTRACT: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. The 10-year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation. According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously.
    Cancer 11/2009; 116(2):432-42. · 5.20 Impact Factor
  • V M Tronnier, D Rasche
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    ABSTRACT: Although surgical ablative procedures can be effective in the management of chronic pain of malignant and non-malignant origin, they are often disregarded as treatment options due to the fact that in the past these procedures were associated with high complication rates. The complications include the development of new neurological deficits and in cases of long-term follow-up, the occurrence of the old or new pain syndromes by deafferentation. On the other hand there exist many less invasive, e.g. neuromodulatory procedures or non-invasive measures (systemic oral or transdermal opioids) which are able to considerably reduce chronic pain. Nevertheless, there remain certain very restricted indications for the use of neuroablative procedures for the treatment of chronic pain even today.
    Der Schmerz 09/2009; 23(5):531-41; quiz 542-3. · 1.02 Impact Factor
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    ABSTRACT: The authors investigated the possibility of improving positioning of stimulation leads in patients with chronic neuropathic peripheral nerve pain and good pain relief from implantation of a peripheral nerve stimulator (PNS). This pilot study includes four patients suffering from Chronic Regional Pain Syndrome type II (CRPS II) or neuropathic mononeuropathy treated with PNS therapy. The affected extremities and corresponding implantation sites were examined using computer tomographic scans (CT), additional CT angiography (CTA), reconstruction techniques and postprocessing procedures. It was possible to prove a close relation between the implanted device and the neurovascular bundle in each of these cases. Thus, indirect lead position control was obtained. Computer tomographic techniques represent a reliable method for the position control of implanted peripheral nerve electrodes. Hence, this procedure should surpass general radiographies in detecting lead displacements.
    Acta Neurochirurgica 05/2009; 151(6):663-7; discussion 667. · 1.55 Impact Factor
  • V.M. Tronnier, D. Rasche
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    ABSTRACT: Obwohl neurodestruktive Verfahren sehr effektiv in der Behandlung von Schmerzen malignen und nichtmalignen Ursprungs sein können, werden sie heute kaum noch durchgeführt. Dies liegt zum einen daran, dass sie in der Vergangenheit mit einer hohen Komplikationsrate verbunden waren. Diese Komplikationen beinhalteten das Auftreten neuer neurologischer Defizite und – bei entsprechend langer Nachbeobachtungszeit – das Wiederauftreten der früheren Schmerzen oder neuer Schmerzen durch eine Deafferentierung. Zum anderen gelingt es, mit weniger invasiven, z.B. neuromodulatorischen oder nichtinvasiven Verfahren (systemische, orale, transdermale Opioide, Koanalgetika) einen großen Teil dieser Schmerzen befriedigend zu reduzieren. Dennoch bestehen auch heute noch bestimmte, sehr eingeschränkte Indikationen für die Durchführung neurodestruktiver Verfahren. Although surgical ablative procedures can be effective in the management of chronic pain of malignant and non-malignant origin, they are often disregarded as treatment options due to the fact that in the past these procedures were associated with high complication rates. The complications include the development of new neurological deficits and in cases of long-term follow-up, the occurrence of the old or new pain syndromes by deafferentation. On the other hand there exist many less invasive, e.g. neuromodulatory procedures or non-invasive measures (systemic oral or transdermal opioids) which are able to considerably reduce chronic pain. Nevertheless, there remain certain very restricted indications for the use of neuroablative procedures for the treatment of chronic pain even today.
    Der Schmerz 01/2009; 23(5):531-543. · 1.02 Impact Factor
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    ABSTRACT: Vagus nerve stimulation (VNS) is an additive treatment option for refractory epilepsy. The electrode is placed on the cervical trunk of the left vagus nerve. In patients who are not suitable for left-sided vagus nerve stimulation (L-VNS) right-sided vagus nerve stimulation (R-VNS) may be as effective. In animal models epilepsy is sufficiently suppressed by R-VNS. In a 16 years old boy suffering from medically refractory psychomotoric seizures with secondary generalisation, L-VNS reduced the frequency of generalized seizures. A deep wound infection required the removal of the system eight weeks later. Cicatrisation did not allow preparation of the left vagus nerve, therefore we implanted R-VNS with sufficient seizure suppression. However, compared to L-VNS, the effect occurred months later and cardiac symptoms were induced by stimulation of the right vagus nerve. R-VNS seems to be an effective and alternative therapy in selected patients responding to L-VNS where a left-sided reimplantation is not possible. Placement and adjustment of the device should be performed under ECG control. Further studies are necessary to compare the efficacy of L-VNS and R-VNS.
    Epilepsy research 10/2008; 82(2-3):232-4. · 2.48 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohen's d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. German Federal Ministry of Education and Research (01GI0201).
    The Lancet Neurology 08/2008; 7(7):605-14. · 23.92 Impact Factor
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    ABSTRACT: Several lines of evidence point to a disturbance of olivo-cerebellar pathways in essential tremor (ET). For example, subjects with ET exhibit deficits in eyeblink conditioning, a form of associative learning which is known to depend on the integrity of olivo-cerebellar circuits. Deep brain stimulation (DBS) of the ventrolateral thalamus is an established therapy for ET. If tremor in ET is related to the same pathology of the olivo-cerebellar system as impaired eyeblink conditioning, one may expect modulation of eyeblink conditioning by DBS. Delay eyeblink conditioning was assessed in 11 ET subjects treated with DBS (ET-DBS subjects) who were studied on two consecutive days with DBS switched off (day 1) and on (day 2). For comparison, 11 age-matched ET subjects without DBS (ET subjects) and 11 age-matched healthy controls were studied. On day 1, eyeblink conditioning was diminished in ET-DBS subjects and in ET subjects compared with controls. When DBS was switched on ET-DBS subjects exhibited conditioning rates within the range of controls on day 2, while ET subjects improved only minimally. Improved eyeblink conditioning in ET-DBS subjects suggests that thalamic DBS counteracts a functional disturbance of olivo-cerebellar circuits which is thought to be responsible for eyeblink conditioning deficits in ET. Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role.
    Experimental Neurology 07/2008; 211(2):387-96. · 4.65 Impact Factor

Publication Stats

3k Citations
365.77 Total Impact Points


  • 2013–2014
    • Universität zu Lübeck
      • Department of Neurosurgery
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2012
    • University of Wuerzburg
      • Department of Neurology
      Würzburg, Bavaria, Germany
  • 1992–2012
    • Universität Heidelberg
      • • Department of Neurology
      • • Abteilung für Neuroradiologie
      • • University Hospital of Internal Medicine
      Heidelburg, Baden-Württemberg, Germany
  • 2009–2011
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2007–2009
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2006
    • Charité Universitätsmedizin Berlin
      • Department of Nephrology
      Berlín, Berlin, Germany
  • 2005
    • Ethianum Klinik Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2001–2004
    • Technische Universität München
      • Neurologische Klinik und Poliklinik
      München, Bavaria, Germany